Biomaterial-enhanced treg cell immunotherapy:A promising approach for transplant medicine and autoimmune disease treatment

Regulatory T cells(Tregs)are crucial for preserving tolerance in the body,rendering Treg immunotherapy a promising treatment option for both organ transplants and autoimmune diseases.Presently,organ transplant recipients must undergo lifelong immunosuppression to prevent allograft rejection,while autoimmune disorders lack definitive cures.In the last years,there has been notable advancement in comprehending the biology of both antigen-specific and polyclonal Tregs.Clinical trials involving Tregs have demonstrated their safety and effectiveness.To maximize the efficacy of Treg immunotherapy,it is essential for these cells to migrate to specific target tissues,maintain stability within local organs,bolster their suppressive capabilities,and ensure their intended function’s longevity.In pursuit of these goals,the utilization of biomaterials emerges as an attractive supportive strategy for Treg immunotherapy in addressing these challenges.As a result,the prospect of employing biomaterial-enhanced Treg immunotherapy holds tremendous promise as a treatment option for organ transplant recipients and individuals grappling with autoimmune diseases in the near future.This paper introduces strategies based on biomaterial-assisted Treg immunotherapy to enhance transplant medicine and autoimmune treatments.

High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma

Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its localization.Chimeric antigen receptor(CAR)T cell immunotherapy has emerged as a powerful strategy to treat cancer.IL-13-receptor-α2(IL13Rα2),present in over 75%of GBMs,has been recognized as an attractive candidate for antiglioblastoma therapy.Here,we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent,therapeutic nanoparticles and CAR T cells modified with a targeted-quadruplemutant of IL13(TQM-13)shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target toxicity.Azide-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile,selective,and high-yielding clicking of the nanoparticles.Nanoparticles clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery.T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T cells.In vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles alone.This work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.